This is a five year renewal application for the Transfusion Medicine/Hemostasis Clinical Research Network (TMHCRN). The mission of the TMH is to launch key clinical trials in the related fields of transfusion medicine, and in treatment of bleeding and bleeding disorders. The range of potential disorders spanned by the TMHCRN is wide, and reflected by the structure of the network into committees devoted to domains within these broad fields. The network is composed of 17 US core sites, a data coordinating center, and a number of consortium and project-specific collaboration partners. The multicenter nature of the network is critical for sample size considerations in studies of rare blood disorders. This application represents a consortium of three Harvard teaching hospitals, with demonstrated capability for network participation and active accrual to the current network studies. To date, the network has launched three active clinical studies, one on optimal platelet transfusion dose in thrombocytopenia, one on treatment of long INR to prevent surgical bleeding, and one on treatment of congenital hemophilia with inhibitors with the targeted anti-B cell agent, rituximab. This renewal application details several studies in the pipeline already, which will be launched during the upcoming five year period. In addition, specific new protocols are proposed, the result of network-wide "think tank" activities during 2006. The plan is to further develop and launch these studies in turn through the steering committee development and approval process, and through the pipeline in turn. (I) a phase III study of fondaparinux versus argatroban in the treatment of isolated heparin induced thrombocytopenia;(II) A randomized trial of epsilon- aminocaproic acid and platelet transfusions vs platelet transfusion alone in the prevention of bleeding in thrombocytopenic patients, and (III) a randomized trial of an oral thrombopoietin-mimetic agent plus standard care, versus standard care, in children with persistent immune thrombocytopenic purpura (ITP). The network serves as a fertile ground for collaborative research, and a particularly important resource for training young physician scientists in patient-oriented research in transfusion medicine and non-malignant hematology, in accordance with recent initiatives of NIH overall, and of NHLBI.